This is a second revision of a competitive renewal to test the hypothesis that the membrane skeleton is an integral structural component of the PMN microbicidal oxidase system and, hence, plays a critical role in assembly of the NADPH-dependent oxidase of human neutrophils. To this end, the proposed studies will address two specific aims: 1) identification of domains of the cytosolic oxidase component p47phox which mediate assembly of the oxidase; and 2) identification of components of the membrane skeleton associated with the assembled oxidase. It is suggested that results from these studies will provide insights concerning the structural determinants which integrate the assembly of an active oxidase with reorganization of the cytoskeleton during PMN stimulation.